1. Field of the Invention
The present invention generally concerns laboratory devices and laboratory methods for separating liquid samples.
The present invention particularly concerns an improvement to a device for separating liquid samples including (i) a first, sample, cylindrical container having an inlet and an outlet opening between which a separation layer is arranged, the outlet opening typically being connected to and enclosed by an outlet spout, fitting within a cylindrical bore of (ii) a second, collecting, container receiving the separated liquid discharged from the outlet spout; the improvement being of the nature of making the cylindrical first container to be both (a) of lesser diameter than is the bore and (b) possessed of features, normally longitudinal exterior protuberances or ribs, that hold it eccentric within the bore, thus permitting that access may be made by hypodermic syringe down the side of the first container to a separated liquid present at the bottom of the second container.
2. Background of the Invention
2.1 General Laboratory Devices and Procedures for Separation of Liquid Samples
The present invention will be seen to concern an improvement to an existing laboratory device commonly called a "miniprep", and to the laboratory procedures for the use of such a device.
A"miniprep" is concerned with the separation of liquid samples into their individual components, the extraction of particular components of a liquid sample, and/or the filtration of a liquid sample. The liquid sample can be, for example, a solution, a colloidal dispersion, or a suspension. The liquid sample is commonly only a few milliliters in volume.
The liquid sample is introduced--typically, for example, by pipette--into a first, sample, container of generally cylindrical form. The cylindrical sample container typically, but not necessarily, narrows to a spout at its lower region.
A separation layer normally in the form of filter paper, glass frit, a membrane, or other material with selective absorption properties is held in, and near the bottom of, the sample container. The liquid sample introduced into and held within the sample container penetrates this separation layer, flows through the spout, and enters into a second, collection, container that is arranged at a distance below the sample container.
The separation normally proceeds liquid drop by liquid drop, typically under (i) the centrifugal force of centrifuging or, else (ii) vacuum suction such as is described in U.S. Pat. No. 5,464,541 for a DEVICE AND METHOD FOR SEPARATING OF LIQUID SAMPLES as is further described below.
The present invention will be seen to concern improvements to "miniprep" containers that are generally centrifuged, and that are of a kind not normally used in vacuum separation (although it is not precluded that they should be so used).
The "miniprep" sample container and collecting container are generally of substantially tubular shape, typically holding but a few milliliters liquid each. (Ergo the "mini".) The separation layer normally abuts the bottom wall of the sample container, which bottom wall has the outlet opening formed therein. The outlet opening normally has a diameter of only a few tenths of a millimeter. The sample container normally fits (i) snugly, or nearly snugly in accordance with the showings of the aforementioned U.S. Pat. No. 5,464,541, and (ii) coaxially within the cylindrical bore of the cylindrical collection container.
The present invention will be seen to change this, and to be opposite in both its (i) fit and (ii) co-axial alignment.
Typically a large number of such sample containers are arranged side by side in rows and in columns, with the arrayed containers being interconnected by a support plate. The penetration of the separation layer in each and all of the sample containers is effected in parallel by force of (i) gravity, (ii) centrifuging, or (iii) vacuum. Each sample container must be withdrawn from its associated collection container after the separation process to expose the separated liquid collected in the bottom of the sample container. Contamination is possible if remaining liquid in the extracted sample containers drips onto other containers of the array, so this must be avoided. The exposed liquid contents in the collection containers are then typically removed with a syringe.
The present invention will be seen to make the laborious step or removing the sample containers from the collection containers unnecessary.
2.2 Specific Previous Patents Concerning Laboratory Devices and Procedures for Separation of Liquid Samples
U.S. Pat. No. 5,464,541--issued Nov. 7, 1995 for a DEVICE AND A METHOD FOR SEPARATING LIQUID SAMPLES to James E. Aysta and assigned to Minnesota Mining and Manufacturing Company, St. Paul, Minn.--concerns a device for separating liquid samples. The device has a sample container the bottom wall of which has an outlet opening. The outlet opening is joined to an outlet spout extending in the axial direction of the sample container. A separation layer is on the bottom wall. A collecting container is arranged abutting and below the sample container. An exchange of air between the interior of the collecting chamber and the environment is possible, yet an escape of liquid is largely inhibited. The contact surface between collecting chamber and sample container, and the end of the outlet spout through which the liquid is discharged, are axially spaced apart. (This will be seen not be the case in the device of the present invention.)
In use a partial vacuum is pulled on the liquid sample. To this end a chamber that may be subjected to a partial vacuum is sealed in an airtight manner with a support plate that supports a number of sample containers. Within the chamber, there are collecting containers associated with each of the sample containers. The collecting containers are fitted into and supported in a rack. The liquid samples are pulled through the separation layer of each sample containers and into the associated collection container under force of the vacuum. Such an apparatus is used, for example, in medical laboratories for the simultaneous separating of a number of liquid samples.
Still earlier multi-well filtration devices have been disclosed in U.S. Pat. Nos. 4,777,021 and 4,427,415. Both reference devices have in common that liquid drops of samples penetrating separation layers will enter a common collecting vessel that is part of a vacuum chamber. The vacuum chamber is again sealed by a support plate interconnecting the individual sample containers arranged in a matrix-like manner. In the reference device for separating liquids, the sample components retained by, or in, the separation layer are of interest in the subsequent tests. The liquid penetrating the separation layer is "lost" for further analyzing purposes. It is frequently necessary for a chemical or bio-polymer separation of samples to individually and selectively catch the sample components that have penetrated the separation layer or have been washed out or removed from the separation layer by applying a solvent. This cannot be realized by using the reference devices.
U.S. Pat. No. 4,902,481 discloses a multi-well filtration apparatus for the assay of microliter quantities. The apparatus has a filter that is positioned in each well on a plate having an open spout positioned in the plate. The spout has a collar on its outer surface extending in a direction perpendicular to the vertical axis of the spout. The collar prevents a liquid droplet from climbing the outer surface of the spout from its open end.
In the '481 patent, the individual collecting containers are only a small distance apart. Due to the distance of the collecting containers to the sample containers, there is a risk that parts of a fluid drop to be received by a collecting container, arranged below a sample container, will enter a neighboring collecting container, thereby contaminating the filtrate thereof. Further, the forming of the drops may not be uniform in the device of U.S. Pat. No. 4,902,481. In particular, it is not uniform when the vacuum in the chamber is released for a short time in order to replace the set of collecting containers accommodated therein by a new one. When releasing the partial vacuum in the chamber, the lower surface of the plate can become wetted by the liquid drops. When a partial vacuum is subsequently generated, relatively large drops will form since sucked-in liquid expands along the lower surface because it is wetted. In this case, a drop may extend up to the annular collar, where it can be sucked off via the gap between the annular collar and the collecting container. Thus, the liquid does not get into the collecting container, but may possibly run into an adjacent collecting container (contamination) or flows along the outside of the respective collecting container.
Contamination of the liquid drops received by the collecting containers is particularly intolerable in the bio-polymer separation of liquid samples since, in this event, the examination of nucleic acids and proteins can be performed after a plurality (25 to 40) of self-replicating cycles, for example in a polymerase chain reaction (PCR), whereby even slight contaminations (contaminations of 1:1000) will be magnified and thus lead to erroneous results in the subsequent analysis.